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In vitro cytotoxicity of glyco-S-nitrosothiols. a novel class of nitric oxide donors.

Abstract
The cytotoxicities of the nitric oxide (NO) donors, S-nitroso-N-acetylpencillamine (SNAP) and three glyco-SNAPs, glucose-1-SNAP, glucose-2-SNAP, and fructose-1-SNAP, towards the human gingival epithelioid S-G cell line and three human carcinoma cell lines derived from tissues of the oral cavity were compared using the neutral red (NR) assay. In general, the glucose-SNAPs were more cytotoxic than SNAP, which, in turn, was more cytotoxic than fructose-1-SNAP. Further studies focused on the response of S-G cells to glucose-2-SNAP. The cytotoxicity of glucose-2-SNAP was attributed to NO, as glucose-2-SNAP (t1/2=20 h at 28 degrees C) aged for 4 days was nontoxic, toxicity was eliminated in the presence of hydroxocobalamin, a specific NO scavenger, and toxicity was not noted with glucose-2-AP (the parent compound used to construct glucose-2-SNAP). Exposure of cells to glucose-2-SNAP resulted in a lessening of the intracellular level of glutathione and cells pretreated with the glutathione-depleter, 1,3-bis-(chloroethyl)-1-nitrosourea, were more sensitive to a subsequent challenge with glucose-2-SNAP. Cytotoxicity of glucose-2-SNAP was lessened upon coexposure with the antioxidants, myricetin, N-acetyl-L-cysteine, and L-ascorbic acid. S-G cells exposed to glucose-2-SNAP exhibited bi- and multinucleation. Death of S-G cells exposed to glucose-2-SNAP apparently occurred by apoptosis, as demonstrated with fluorescence microscopy by the appearance of brightly stained, hypercondensed chromatin in spherical cells and of membrane blebbing and by the DNA-ladder of oligonucleosome-length fragments noted with gel electrophoresis. In comparison with other classes of NO donors the sequence of toxicity towards S-G cells was S-nitrosoglutathione>glucose-SNAPs>SNAP, sodium nitroprusside>spermine NONOate>DPTA NONOate>DETA NONOate>fructose-1-SNAP>>SIN-1.
AuthorsH Babich, H L Zuckerbraun
JournalToxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 15 Issue 3 Pg. 181-90 (Jun 2001) ISSN: 0887-2333 [Print] England
PMID11377090 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Free Radicals
  • Nitric Oxide Donors
  • Nitroso Compounds
  • S-nitro-N-acetylpenicillamine
  • Fructose
  • Nitric Oxide
  • Penicillamine
  • Glucose
Topics
  • Antioxidants (pharmacology)
  • Cell Line
  • Cell Survival (drug effects)
  • Electrophoresis, Agar Gel
  • Epithelial Cells (drug effects)
  • Free Radicals
  • Fructose
  • Gingiva (drug effects)
  • Glucose
  • Humans
  • Microscopy, Fluorescence
  • Nitric Oxide (metabolism)
  • Nitric Oxide Donors (pharmacology)
  • Nitroso Compounds (chemical synthesis, pharmacology)
  • Penicillamine (analogs & derivatives, pharmacology)
  • Tumor Cells, Cultured

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